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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Methionine adenosyltransferase II beta subunit gene expression provides a proliferative advantage in human hepatoma
Autor(es) : Martinez-Chantar, M.L. (María Luz)
Garcia-Trevijano, E.R. (Elena R.)
Latasa, M.U. (María Ujué)
Martin-Duce, A. (Antonio)
Fortes, P. (Puri)
Caballeria, J. (Juan)
Avila, M.A. (Matías Antonio)
Mato, J.M. (José María)
Palabras clave : Carcinoma, Hepatocellular
Liver Neoplasms
Methionine Adenosyltransferase/genetics
Fecha incorporación: 2003
Editorial : WB Saunders
Versión del editor: http://www.sciencedirect.com/science/article/pii/S0016508503000659
ISSN: 1528-0012
Cita: Martinez-Chantar ML, Garcia-Trevijano ER, Latasa MU, Martin-Duce A, Fortes P, Caballeria J, et al. Methionine adenosyltransferase II beta subunit gene expression provides a proliferative advantage in human hepatoma. Gastroenterology 2003 Apr;124(4):940-948.
Resumen
BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes S-adenosylmethionine, MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues. In liver, MAT2A expression associates with growth, dedifferentiation, and cancer. Here, we identified the beta subunit as a regulator of proliferation in human hepatoma cell lines. The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the MAT2A product) for methionine and to render the enzyme more susceptible to S-adenosylmethionine inhibition. METHODS: Methionine adenosyltransferase II alpha2 and beta subunit expression was analyzed in human and rat liver and hepatoma cell lines and their interaction studied in HuH7 cells. beta Subunit expression was up- and down-regulated in human hepatoma cell lines and the effect on DNA synthesis determined. RESULTS: We found that beta subunit is expressed in rat extrahepatic tissues but not in normal liver. In human liver, beta subunit expression associates with cirrhosis and hepatoma. beta Subunit is expressed in most (HepG2, PLC, and Hep3B) but not all (HuH7) hepatoma cell lines. Transfection of beta subunit reduced S-adenosylmethionine content and stimulated DNA synthesis in HuH7 cells, whereas down-regulation of beta subunit expression diminished DNA synthesis in HepG2. The interaction between methionine adenosyltransferase II alpha2 and beta subunit was demonstrated in HuH7 cells. CONCLUSIONS: Our findings indicate that beta subunit associates with cirrhosis and cancer providing a proliferative advantage in hepatoma cells through its interaction with methionine adenosyltransferase II alpha2 and down-regulation of S-adenosylmethionine levels.
Enlace permanente: http://hdl.handle.net/10171/23277
Aparece en las colecciones: DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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Fichero:  Gastroenterology2003_124_940.pdf
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